The production of endogeneous leukemia viruses (MuLV) in mice of high leukemic strains is controlled by multiple non-linked dominant loci. Biological studies and analysis by molecular hybridization demonstrate that in the AKR strain these loci are the integrated DNA proviruses of endogeneous MuLV. The presence of genetically integrated "V" genes in mice of high leukemic strains results in the constitutive production of high titers of MuLV throughout their life spans. Although persistant expression of MuLV is a characteristic of high leukemic strains, the development of overt leukemia in these mice does not occur until approximately one year of age. This delay in the onset of disease is one of the outstanding enigmas in the understanding of leukemogenesis. The purpose of this research project is to investigate the age-related changes that occur in the expression of MuLV in the lymphoid tissues of AKR mice. In the initial phases of this project we will isolate, clone, and characterize the viruses that are produced by preleukemic and leukemic lymphocytes. Isolates of AKR virues will be analyzed for biological, biochemical, and serological relatedness; in addition, each of these viruses will be assayed for oncogenicty in vivo. This analysis will be directed at determining the virus or viruses that are the proximal carcinogens in spontaneous leukemogenesis. Other studies will investigate the expression of these viruses in lymphocytes during the aging process. Cells expressing viral proteins on their cell surface will be isolated by the fluorescence-activated cell sorter. These cells will be examined for the types of virus they produce and for their disposition towards malignant transformation. In subsequent studies, we will examine biochemical and serological properties of these virus-coded cell surface antigens. Efforts will be made to use these cell surface proteins as markers for the expression of individual viral genomes.